Tubulysins are a group of powerful inhibitors of tubulin polymerization. Tubulysins are useful in treating diseases and disease states that include pathogenic cell populations, such as cancer. Generally, tubulysins are linear tetrapeptides consisting of N-methyl pipecolic acid (Mep), isoleucine (Ile), an unnatural aminoacid called tubuvalin (Tuv), and either an unnatural aminoacid called tubutyrosine (Tut, an analog of tyrosine) or an unnatural aminoacid called tubuphenylalanine (Tup, an analog of phenylalanine), as shown in the following table:
 FactorR1TA(CH3)2CHCH2OHBCH3(CH2)2OHCCH3CH2OHD(CH3)2CHCH2HECH3(CH2)2HFCH2CH3HG(CH3)2C═CHOHHCH3HICH3OHTwo particular species of mycobacteria synthesize tubulysins in high titer during fermentation. However, each species generally synthesizes a mixture of tubulysin factors, and that mixture differs between each of those mycobacteria species. For example, one species, Archangium gephyra, produces as the main component factors tubulysins A, B, C, G, and I, each of which may be identified by its including the Tut residue. In contrast, another species, Angiococcus disciformis, produces as the main component factors tubulysins D, E, F, and H, each of which may be identified by its including the Tup residue.
Such bacterial fermentations are convenient sources of tubulysins. However, because the mycobacteria produce only certain tubulysins, and/or mixtures of tubulysins, processes are needed for interconverting those tubulysins to the desired factors for medicinal and pharmacological uses. In addition, processes are needed for preparing novel tubulysins, tubulysin analogs, and tubulysin derivatives for medicinal and pharmacological uses.